ABSTRACT
Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.
ABSTRACT
This study was aimed to investigate renal protective effects and mechanism of Gui-Zhi(GZ) decoction in hyperuricemic mice.Potassium oxonate was used to induce hyperuricemia mouse model.Mice were randomly divided into 6 groups,which were the blank control group,model group,allopurinol group (5 mg·kg-1) and GZ decoction group (900,1 799 and 3 598 mg·kg-1).Hematoxylin eosin staining was used to observe the histopathological changes of renal tissues in mice.Commercial assay kits were used to measure levels of uric acid (UA),creatinine (Cr) and blood urea nitrogen (BUN) in serum and urine,as well as the xanthine oxidase (XOD) activity in liver.Renal protein levels of urate transporter 1 (URAT1),glucose transporter 9 (GLUT9),ATP-binding cassette G member 2 (ABCG2),organic cation transporter 1 (OCT1),OCT2,organic cation/carnitine transporter 1 (OCTN1) and OCTN2 were detected by western blot.The results showed that compared with the model group,GZ decoction can obviously decrease serum levels of UA,Cr and BUN,increase urine levels of UA and Cr,resulting in the elevation of fractional excretion of UA in hyperuricemic mice.Additionally,GZ decoction obviously inhibited hepatic XOD activity in hyperuricemic mice.Furthermore,GZ decoction downregulated renal URAT1 and GLUT9 protein levels,upregulated renal ABCG2,as well as OCT1,OCT2,OCTN1 and OCTN2 protein levels in hyperuricemic mice.It was concluded that GZ decoction had hypouricemic and renal protective effects in hyperuricemic mice,which might be associated with the reduction of UA production via inhibiting hepatic XOD activity,promoting UA and other organic ion excretion via regulating renal organic ion transporter protein levels.
ABSTRACT
Objective To evaluate the antigenic specificity of the enolase.Methods and Results The results included:(1)Western blot analysis demonstrated that enolase was a main protein in the nonglyco-proteins of C.albicans which could react with the serum of C.albicans infected rabbit.(2)The purified enolase was used to immunize rabbit for producing anti-enolase serum,and the hig hest titer of polyclonal antibody against enolase was up to 1:6400with enzyme-linked immunoadso rbent assay(ELISA).(3)Compared with three other polyclonal antibodies,anti-enola se antibody showed high specificity in detecting C.albicans antigen.Conclusion Enolase as a specific antigen,is worthy of further investigation in C.albicans cell.